Olodaterol (trade name Striverdi Respimat) is an ultra- long-acting β adrenoreceptor agonist (ultra-LABA) used as an inhalation for treating people with

chronic obstructive pulmonary disease Chronic obstructive pulmonary disease (COPD) is a type of progressive lung disease characterized by long-term respiratory symptoms and airflow limitation. The main symptoms include shortness of breath and a cough, which may or may not produce ...

(COPD). It is manufactured by

Boehringer Ingelheim C.H. Boehringer Sohn AG & Co. is the parent company of the Boehringer Ingelheim group, which was founded in 1885 by Albert Boehringer in Ingelheim am Rhein, Germany. As of 2018, Boehringer Ingelheim is one of the world's largest pharmaceutical ...

.Striverdi

Medical uses

Olodaterol is a once-daily maintenance

bronchodilator A bronchodilator or broncholytic (although the latter occasionally includes secretory inhibition as well) is a substance that dilates the bronchi and bronchioles, decreasing resistance in the respiratory airway and increasing airflow to the lun ...

treatment of airflow obstruction in people with COPD. While it appears to reduce COPD exacerbations it does not appear to alter the speed at which a person's lungs worsen or alter their life expectancy. , olodaterol is not approved for the treatment of

asthma Asthma is a long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wheezing, cou ...

. It is administered in an

inhaler An inhaler (also known as a puffer, pump or allergy spray) is a medical device used for delivering medicines into the lungs through the work of a person's breathing. This allows medicines to be delivered to and absorbed in the lungs, which prov ...

called

Respimat Respimat, also known as Respimat Soft Mist Inhaler, is a drug delivery device used for the treatment of asthma, chronic obstructive pulmonary disease (COPD), and other respiratory conditions. Its developer, Boehringer Ingelheim, is currently con ...

Soft Mist Inhaler.

Adverse effects

Adverse effects generally were rare and mild in clinical studies. Most common, but still affecting no more than 1% of patients, were nasopharyngitis (running nose),

dizziness Dizziness is an imprecise term that can refer to a sense of disorientation in space, vertigo, or lightheadedness. It can also refer to disequilibrium or a non-specific feeling, such as giddiness or foolishness. Dizziness is a common medical c ...

and

rash A rash is a change of the human skin which affects its color, appearance, or texture. A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, cr ...

. To judge from the drug's mechanism of action and from experiences with related drugs,

hypertension Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...

(high blood pressure),

tachycardia Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal (su ...

(fast heartbeat),

hypokalemia Hypokalemia is a low level of potassium (K+) in the blood serum. Mild low potassium does not typically cause symptoms. Symptoms may include feeling tired, leg cramps, weakness, and constipation. Low potassium also increases the risk of an abno ...

(low blood levels of

potassium Potassium is the chemical element with the symbol K (from Neo-Latin ''kalium'') and atomic number19. Potassium is a silvery-white metal that is soft enough to be cut with a knife with little force. Potassium metal reacts rapidly with atmosphe ...

), shaking, etc., might occur in some patients, but these effects have rarely, if at all, been observed in studies.

Interactions

Based on theoretical considerations, co-application of other beta-adrenoceptor agonists, potassium lowering drugs (e.g.

corticosteroid Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are involv ...

s, many

diuretic A diuretic () is any substance that promotes diuresis, the increased production of urine. This includes forced diuresis. A diuretic tablet is sometimes colloquially called a water tablet. There are several categories of diuretics. All diuretics in ...

s, and

theophylline Theophylline, also known as 1,3-dimethylxanthine, is a phosphodiesterase inhibiting drug used in therapy for respiratory diseases such as chronic obstructive pulmonary disease (COPD) and asthma under a variety of brand names. As a member of the ...

tricyclic antidepressant Tricyclic antidepressants (TCAs) are a class of medications that are used primarily as antidepressants, which is important for the management of depression. They are second-line drugs next to SSRIs. TCAs were discovered in the early 1950s and wer ...

s, and

monoamine oxidase inhibitor Monoamine oxidase inhibitors (MAOIs) are a class of drugs that inhibit the activity of one or both monoamine oxidase enzymes: monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). They are best known as effective antidepressants, espe ...

s could increase the likelihood of adverse effects to occur.

Beta blocker Beta blockers, also spelled β-blockers, are a class of medications that are predominantly used to manage cardiac arrhythmia, abnormal heart rhythms, and to protect the heart from a second myocardial infarction, heart attack after a first heart ...

s, a group of drugs for the treatment of

(high blood pressure) and various conditions of the heart, could reduce the efficacy of olodaterol. Clinical data on the relevance of such interactions are very limited.

Pharmacology

Mechanism of action

Like all β adrenoreceptor agonists, olodaterol mimics the effect of

epinephrine Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands and ...

at β₂ receptors in the lung, which causes the

bronchi A bronchus is a passage or airway in the lower respiratory tract that conducts air into the lungs. The first or primary bronchi pronounced (BRAN-KAI) to branch from the trachea at the carina are the right main bronchus and the left main bronchus. ...

to relax and reduces their resistance to airflow. Olodaterol is a nearly full β₂ agonist, having 88%

intrinsic activity Intrinsic activity (IA) and efficacy refer to the relative ability of a drug-receptor complex to produce a maximum functional response. This must be distinguished from the affinity, which is a measure of the ability of the drug to bind to its mol ...

compared to the gold standard

isoprenaline Isoprenaline, or isoproterenol (brand name: Isoprenaline Macure), is a medication used for the treatment of bradycardia (slow heart rate), heart block, and rarely for asthma. It is a non-selective β adrenoceptor agonist that is the isopropylam ...

/isoproterenol). Its

half maximal effective concentration ] Half maximal effective concentration (EC50) is a measure of the concentration of a drug, antibody or toxicant which induces a Stimulus%E2%80%93response_model, response halfway between the baseline and maximum after a specified exposure time. Mo ...

(EC₅₀) is 0.1 Molar concentration, nM. It has a higher ''

in vitro ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in biology an ...

'' selectivity for β₂ receptors than the related drugs

formoterol Formoterol, also known as eformoterol, is a long-acting β2 agonist (LABA) used as a bronchodilator in the management of asthma and chronic obstructive pulmonary disease (COPD). Formoterol has an extended duration of action (up to 12 h) co ...

and

salmeterol Salmeterol (sold in China as Qitai) is a long-acting β2 adrenergic receptor agonist (LABA) used in the maintenance and prevention of asthma symptoms and maintenance of chronic obstructive pulmonary disease (COPD) symptoms. Symptoms of bronchos ...

: 241-fold versus β₁ and 2299-fold versus β₃ adrenergic receptors. The high β₂/β₁ selectivity may account for the apparent lack of tachycardia in clinical trials, which is mediated by β₁ receptors on the heart.

Pharmacokinetics

Olodaterol is substantially metabolized by glucuronidation (

UGT2B7 UGT2B7 (UDP-Glucuronosyltransferase-2B7) is a phase II metabolism isoenzyme found to be active in the liver, kidneys, epithelial cells of the lower gastrointestinal tract and also has been reported in the brain. In humans, UDP-Glucuronosyltrans ...

UGT1A1 UDP-glucuronosyltransferase 1-1 also known as UGT-1A is an enzyme that in humans is encoded by the ''UGT1A1'' gene. UGT-1A is a uridine diphosphate glucuronosyltransferase (UDP-glucuronosyltransferase, UDPGT), an enzyme of the glucuronidation path ...

UGT1A9 UDP-glucuronosyltransferase 1-9 is an enzyme that in humans is encoded by the ''UGT1A9'' gene. Function This gene encodes a UDP-glucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such a ...

) and ''O''-demethylation (

CYP2C8 Cytochrome P4502C8 (abbreviated CYP2C8), a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the body. Cytochrome P4502C8 also possesses epoxygenase activity, i.e. it metabolizes long-cha ...

CYP2C9 Cytochrome P450 family 2 subfamily C member 9 (abbreviated CYP2C9) is an enzyme protein. The enzyme is involved in metabolism, by oxidation, of both xenobiotics, including drugs, and endogenous compounds, including fatty acids. In humans, the prote ...

Pharmadynamics

Once bound to a β₂ receptor, an olodaterol molecule stays there for hours — its dissociation half-life is 17.8 hours —, which allows for once-a-day application of the drug like with

indacaterol Indacaterol is an ultra-long-acting beta-adrenoceptor agonist developed by Novartis. It needs to be taken only once a day, unlike the related drugs formoterol and salmeterol. It is licensed only for the treatment of chronic obstructive pulmonary d ...

. Other related compounds generally have a shorter duration of action and have to be applied twice daily (e.g. formoterol, salmeterol). Still others (e. g. salbutamol/аlbuterol,

fenoterol Fenoterol is a β adrenoreceptor agonist. It is classed as sympathomimetic β2 agonist and an inhaled bronchodilator asthma medication. Fenoterol is produced and sold by Boehringer Ingelheim as Berotec N and in combination with ipratropium as ...

) have to be applied three or four times a day for continuous action, which can also be an advantage for patients who need to apply β₂ agonists only occasionally, for example in an

attack.

History

On 29 January 2013 the U.S.

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...

(FDA) Pulmonary-Allergy Drugs Advisory Committee (PADAC) recommended that the clinical data included in the new drug application (NDA) for olodaterol provide substantial evidence of safety and efficacy to support the approval of olodaterol as a once-daily maintenance

treatment for airflow obstruction in patients with COPD. On 18 October 2013 approval of olodaterol in the first three European countries — the United Kingdom, Denmark and Iceland — was announced by the manufacturer. On July 31, 2014 the U.S. Food and Drug Administration approved Striverdi Respimat (olodaterol inhalation spray) to treat patients with

(COPD), including chronic bronchitis and/or emphysema that are experiencing airflow obstruction.

References

External links

Striverdi package leaflet (UK)
{{Drugs for obstructive airway diseases Long-acting beta2-adrenergic agonists Benzoxazines Phenol ethers Phenylethanolamines Substituted amphetamines